Ten-eleven　translocation　1　(TET1),　a　widely　reported　DNA　demethylation　protein,　has　been　associated　with　tumorigenesis　and　metastasis.　However,　whether　TET1　is　an　oncogene　or　tumor　suppressor　gene　has　been　controversial;　the　mechanism　of　how　TET1　affects　cancer　progression　remains　unclear.　The　current　study　aims　to　investigate　how　TET1　is　changed　in　the　tumor　microenvironment　and　to　explore　the　mechanisms　of　how　TET1　affects　colon　cancer　progression.　Because　hypoxia　prevails　on　solid　tumors,　we　established　an　important　connection　between　hypoxia　and　DNA　demethylation　in　tumorigenesis.　By　qPCR　and　RNA　interference　(RNAi)　technology,　we　found　that　hypoxia　increased　TET1　expression　with　a　hypoxia-inducible　factor-1-alpha　(HIF-1　alpha)-dependent　manner.　By　CHIP-qPCR　and　pyrosequencing　technology,　we　demonstrated　that　TET1　regulated　the　target　gene　expression　of　HIF-1　alpha　through　HIF-1　alpha　binding　to　hypoxia-responsive　elements　(HREs),　and　HIF-1　alpha　binding　to　HREs　depended　on　CpG　methylation　levels.　By　Cell　Counting　Kit-8　(CCK-8)　and　transwell　assay,　we　showed　that　loss　of　TET1　did　not　affect　cell　proliferation　but　inhibited　migration.　We　also　identified　two　novel　gene　mutants　of　TET1　in　120　paired　tumor/normal　tissue　specimens　by　DNA　sequencing　and　found　that　TET1　E2082K　mutant　blocked　the　TET1-enhanced　cell　migration.　Our　results　showed　that　the　downregulation　of　TET1　rescued　the　abnormally　high　levels　of　gene　expression　resulting　from　hypoxia　in　tumors　and　reduced　the　migration　activity　of　tumor　cells,　suggesting　a　therapeutic　role　by　interference　with　TET1　in　colon　cancer　treatment.　By　demonstrating　that　hypoxia　upregulated　TET1　and　that　TET1　drove　HIF-1　alpha-responsive　genes,　we　showed　that　an　epigenetic　mechanism　and　tumor　microenvironment-driven　models　coexisted　and　mutually　affected　colon　cancer.